ABSTRACT
Objective To explore the regulatory role of fat mass and obesity-associated protein(FTO)and serine-threonine kinase protein kinase D2(PRKD2)in progression of diabetic kidney disease(DKD)and its regulatory mechanisms.Methods DKD model in vitro was constructed by podocytes(MPC5 cells)treated with high glucose(HG,35 mmol/L glucose)for 24 h.HG-induced MPC5 cells were transfected with FTO overexpression vector(pcDNA-FTO)and PRKD2 overexpression vector(pcDNA-PRKD2),or empty vector.The overexpression efficiency of FTO and PRKD2 were detected with RT-qPCR.MeRIP was used to detect the N6-methyladenosine(m6A)modification level of PRKD2 mRNA.The activity of Caspase-3 and the secretion of IL-6,TNF-α and monocyte chemotactic protein-1(MCP-1)were detected by ELISA.Cell apoptosis rate was analyzed by flow cytometry.The protein levels of FTO and PRKD2,as well as the key proteins in SIRT1/HIF-1α pathway,were evaluated by Western blot.Pearson analysis was used to analyze the correlation between FTO levels and PRKD2 levels.Results Compared with the control group without HG-induction,the protein expression of FTO(0.51±0.04 vs 1.00±0.03)and PRKD2(0.45±0.03 vs 1.01±0.04)was significantly down-regulated in HG-induced podocytes,and the differences were statistically significant(t=13.17,16.76,all P＜0.001).FTO protein levels were positively correlated with PRKD2 protein levels in HG-induced podocytes(r2=0.705 1,P＜0.001).Compared with the vector group,the m6A levels of PRKD2 mRNA(0.56±0.09 vs 1.01±0.13)in the pcDNA-FTO group were decreased,and the mRNA levels of PRKD2(3.16±0.14 vs 1.03±0.02)were increased,with significant differences(t=51.37,11.82,all P＜0.001).Compared with the control group(IL-6:512.76±61.85 pg/ml,TNF-α:28.17±2.83 pg/ml,MCP-1:157.31±17.69 pg/ml)and the vector group(IL-6:498.41±87.51 pg/ml,TNF-α:26.35±5.47 pg/ml,MCP-1:165.52±16.87 pg/ml),the secretion of IL-6(301.86±21.85 pg/ml),TNF-α(11.06±4.12 pg/ml)and MCP-1(81.45±9.03 pg/ml)were significantly decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=7.51,10.47,61.97,all P＜0.01).Compared with the control group(caspase-3 activity:689.65±79.5 U/L,cell apoptosis:22.31%±2.69%)and the vector group(Caspase-3 activity:715.91±113.58 U/L,cell apoptosis:21.07%±3.28%),Caspase-3 activity(437.64±104.76 U/L)and the rate of apoptosis(8.41%±3.15%)were significantly decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=2.35,79.13,all P＜0.01).Compared with the control group(SIRT1:1.01±0.05,HIF-1α:1.03±0.07)and the vector group(SIRT1:0.97±0.05,HIF-1α:1.02±0.03),SIRT1 protein levels(3.51±0.15)were increased and HIF-1α protein levels(0.37±0.07)were decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=31.54,8.31,all P＜0.01).Conclusion FTO-mediated and m6A-modified PRKD2 suppresses inflammation and apoptosis in HG-induced podocytes through the SIRT1/HIF-1 pathway.
ABSTRACT
Chronic Guillain-Barre syndrome, also known as chronic inflammatory demyelinating polyradiculoneuropathy(CIDP), is an immune-mediated demyelinating peripheral neuropathy. This article analyzes the clinical data of a CIDP patient presenting primarily with limb numbness, pain, and weakness. Along with literature review, this study explores the differential diagnosis between CIDP and diabetic peripheral neuropathy in terms of the pathogenesis, clinical manifestations, laboratory tests, and treatment.
ABSTRACT
Objective To explore the relationship between the stimulated thyroglobulin ( sTg) and site, number and diameter of metastatic lesions in patients with differentiated thyroid carcinoma (DTC) before the first 131 I treatment, and to evaluate the predictive value of sTg for different metastatic sites. Methods A total of 567 DTC patients (179 males, 388 females; age: (45.3±12.3) years) who received the first 131Ⅰ treatment between January 2012 and June 2017 were included. Thyroglobulin antibody (TgAb), sTg and thyroid stimulating hormone ( TSH) were determined within 1 week before 131 I treatment. Metastases were detected by ultrasonography, CT or 18 F-fluorodeoxyglucose ( FDG ) PET/CT, 131 I whole-body scan, SPECT/CT imaging and pathology. sTg levels of patients with different metastatic sites and different metasta-sis numbers or lesion diameters were compared ( Kruskal-Wallis H test) . Spearman correlation analysis was performed on the number, diameter and sTg level of metastases. The receiver operating characteristic ( ROC) curve was used to explore the predictive value of sTg before the first 131 I treatment for DTC metasta-sis. Results The median values of sTg in the bone, lung, lymph node metastases groups and non-metasta-sis group were 500.00, 104.40, 27.45, 2.39μg/L, respectively, and there were significant differences, ex-cept for bone and lung metastases groups ( H range: -294.605 to 175.162, all P<0.05) . The sTg levels of lung metastasis group and lymph node metastasis group were both decreased by the order of metastasis num- bers (≥3, =2, =1;H range:-57.887 to 48.763, all P<0.05) . As to the diameter of metastases, the sTg levels of >2.0 cm, 1.1-2.0 cm, and≤1.0 cm subgroups in the lung metastasis group and lymph node me-tastasis group were also decreased in order ( H range: -69.935 to 61.043, all P<0.05) . Spearman correla-tion analysis showed that the number ( rs=0.568, 0.606) and diameter ( rs=0.806, 0.664) of the metasta-ses in the lung and lymph node metastases group were positively correlated with sTg (all P<0.05). Areas under ROC curves for sTg to predict bone, lung and lymph node metastasis were 0.935, 0.843 and 0.791 re-spectively. The threshold values were 197. 65, 23. 21 and 10. 96 μg/L respectively. The sensitivities and the specificities were 91.70％, 79.60％, 67.20％ and 97.20％, 80.80％, 82.70％ respectively. Conclusions Tg level before the first 131 I treatment has a certain predictive value for the metastasis, metastatic site and num-ber or diameter in DTC patients.